The new Alzheimer's Disease Research Center (ADRC), at the University of California at San Francisco (UCSF) has made remarkable progress in just four years, developing new diagnostic approaches to dementia, supporting exciting translational and basic science research and providing training and education at a local and national level. We remain committed to four overarching aims: 1) to explore heterogeneous presentations of dementia in the early stages;2) to train new basic and translational science leaders in dementia;3) to educate regarding the non-AD dementias and atypical presentations of AD using conferences and novel web-based approaches;and 4) to bridge the gap between clinical and laboratory studies in dementia by supporting new treatment efforts for AD, FTLD and CJD. With renewal, we will develop better ways to diagnose patients with early FTLD, CBD, PSP, CJD and atypical AD. We will catalyze the development of rational therapies for FTLD with ubiquitin-TDP-43 inclusions, FTLD with tau inclusions, and FTLD associated with progranulin mutations. To generate successful new therapies, we will create effective animal models of disease (Farese project 3) and enhance the accuracy of early diagnosis using our Clinical Core and novel imaging approaches (Seeley project 1). We will involve investigators at the Gladstone Institute such as Lennart Mucke (project 2), Yadong Huang, Li Can, and Robert Mahley in the evaluation of ADRC tissue to bring laboratory findings to the clinic. We will also interact with the CJD drug development program in the Prusiner and DeArmond laboratories by providing well-characterized patients and biosamples. By developing an internet-based approach to education, we will reach tens of thousands of people every year, educating them about dementia, its symptoms, causes and available treatments. We will also host novel and exciting conferences and retreats that generate enthusiasm for our field. To spearhead dementia research, we will continue to attract, train and nurture future leaders in neurodegenerative disease, both in clinical and basic science research. To address the inequalities among aging minority populations, we will develop a unique cohort of Chinese-American patients and integrate this community into our treatment efforts. To understand why some people are able to stave off dementia, we will develop a large healthy aging cohort that will participate in new preventative research efforts. Finally, we will create ideal data management approaches for neurodegenerative conditions that will be shared with other ADRCs, beginning with UC-Davis.